crossing96/oncoscreening huggingface dataset:
An overview of the effect of linoleic and conjugated-linoleic acids on the growth of several human tumor cell lines.	Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic.	bladder
Genomic organisation of the human MDM2 oncogene and relationship to its alternatively spliced mRNAs.	The MDM2 proto-oncogene, which encodes a protein that binds to the p53 tumour suppressor, has been found amplified and overexpressed in a range of human tumours. Although the human MDM2 cDNA sequence has been reported, the genomic organisation of the human gene has not been documented. We have previously reported the detection of five alternative internally deleted MDM2 transcripts in human tumours and suggested these may represent alternatively spliced forms. Here we demonstrate two novel MDM2 transcripts with internal deletions, using RT-PCR followed by sequencing. To definitively ascribe these variant transcript forms to alternative splicing, and to explore associated mechanisms, we have determined the intron--exon organisation of the human genomic sequence. The human MDM2 gene spans approximately 33 kb and is divided into 12 exons. Exon sizes range from 50 to > or =1161 bp and intron sizes vary from 121 to approximately 7000 bp. The positions of intron--exon boundaries are compared with the deletion junctions of the multiple-sized transcripts and discussed in relation to alternative splicing mechanism.	bladder
NMP-22 for bladder cancer screening and surveillance.	In 2004, more than 56,000 Americans will be diagnosed with bladder cancer (American Cancer Society, 2004). Urethrocystoscopy is considered the gold standard for bladder cancer diagnosis, but it is not a screening test. Researchers have been challenged to develop a noninvasive urine test that reliably differentiates hematuria associated with bladder cancer from that associated with nonmalignant etiologies. Several well-established and some novel tests for bladder cancer screening diagnosis and surveillance, including urinalysis, voided cytology, and the Nuclear Matrix Protein 22 (NMP-22) assay, one of a growing number of assays developed as a specific, sensitive noninvasive test for bladder cancer, are reviewed. Until the sensitivity of the NMP-22 is improved, or another urine assay emerges that provides significantly greater sensitivity while maintaining adequate specificity, urethrocystoscopy will remain the reference test for detecting and diagnosing bladder cancer and its recurrence.	bladder
Association between volume and charges for most frequently performed ambulatory and nonambulatory surgery for bladder cancer. Is more cheaper?	PURPOSE: We investigated the relationship between provider volume and charges for transurethral bladder tumor resection (TURBT) and radical cystectomy in patients with bladder cancer. MATERIALS AND METHODS: The National Inpatient Sample (1988 to 1999) of the Health Care Utilization Project, and State Ambulatory Surgery Databases for Wisconsin and Florida (2000 data set) were used for analysis. All patients with bladder cancer who had undergone radical cystectomy or TURBT as the principal procedure were identified. Hospitals and surgeons were categorized into terciles of volume based on the average number performed per year. The average hospital charge per discharge/procedure corrected to 2000 levels was calculated. One-way ANOVA with the Bonferroni correction was used to compare charges between different volume levels. RESULTS: A total of 13,498 patients who underwent radical cystectomy and 5,954 who underwent TURBT were included in the analysis. Charges for radical cystectomy were 5,648 USD lower at high volume hospitals than at low volume hospitals (p <0.001). High volume surgeons were 2,976 USD less expensive than low volume surgeons (p =0.054). For TURBT total hospital charges at high volume hospitals were 1,013 USD more than at low volume hospitals (p <0.0001), while average total hospital charges for procedures performed by high volume surgeons were 919 USD less compared to low volume surgeons (p <0.0001). CONCLUSIONS: High risk inpatient procedures for bladder cancer such as cystectomy, which are more influenced by systems of care, are less expensive to perform at high volume centers. Lower risk ambulatory procedures for bladder cancer, such as TURBT, which are not influenced by systems of care, may be more cost efficiently performed by high volume surgeons at low volume centers.	bladder
Treatment of urethral recurrence following radical cystectomy and ileal bladder substitution.	PURPOSE: With the introduction of orthotopic bladder substitution after radical cystectomy in patients with invasive bladder cancer urethral recurrences have become a therapeutic challenge. MATERIALS AND METHODS: We retrospectively evaluated our patients with urethral recurrences treated with a urethra sparing approach after orthotopic bladder substitution. Depending on the extension of recurrence and eventual concomitant metastases patients were treated with urethrectomy, no treatment, systemic chemotherapy or intraurethral bacillus Calmette-Guerin (BCG). Three times the common dose of BCG (ImmuCyst, Aventis, Paris, France or OncoTICE, Organon, West Orange, New Jersey) in 150 ml NaCl 0.9% was used for intraurethral BCG perfusion therapy according to an institutional protocol using a modified Foley catheter. This regimen was repeated weekly for 6 weeks and patients were followed prospectively. RESULTS: Between 1985 and 2001, 15 of 371 patients (4%) who received an orthotopic bladder substitute had urethral recurrence. Two patients were treated with systemic chemotherapy (methotrexate, vinblastine, doxorubicin and cisplatin) alone due to metastatic disease and 10 received intraurethral BCG therapy. Five of 6 patients (83%) with carcinoma in situ remained free of recurrence following treatment with BCG, while in 4 with papillary or invasive disease treatment failed. Three patients underwent urethrectomy, including 2 following failed BCG therapy for papillary disease. CONCLUSIONS: Carcinoma in situ urethral recurrence following orthotopic bladder substitution can be treated successfully with intraurethral BCG perfusion therapy in approximately 80% of patients. However, papillary and invasive transitional cell urethral recurrence should be treated with urethrectomy.	bladder
Interim results from a national multicenter phase II trial of combination bacillus Calmette-Guerin plus interferon alfa-2b for superficial bladder cancer.	PURPOSE: Interim results are provided from a large multicenter trial of combination bacillus Calmette-Guerin (BCG) plus interferon (IFN) alfa-2b for BCG naive (BCG-N) and previous BCG failure (BCG-F) cases of superficial bladder cancer. MATERIALS AND METHODS: A total of 490 patients enrolled from May 1999 to May 2000 with a median of 24 months of followup were analyzed. The BCG-N group (259) was treated with a 6-week induction course of standard dose BCG plus 50 million units of IFN followed by 3, 3-week maintenance cycles of reduced dose BCG (1/3 to 1/10) plus 50 million units IFN at 3, 9 and 15 months after induction. The BCG-F group (231) was treated similarly except induction therapy began at a decreased (1/3 to 1/10) BCG dose. RESULTS: The simple tumor recurrence rates for BCG-N and BCG-F groups were 40% and 52%, and the Kaplan-Meier estimates for disease freedom at 24 months were 57% and 42%, respectively. Progression to muscle invasion occurred in 5% and 4.3% while metastasis occurred in 2.3% and 2.6%, respectively. In each group 3.9% of patients underwent cystectomy and 2 patients in each group died of bladder cancer. Serious adverse events occurred in 5.5% with infection related serious adverse events being less prevalent in the BCG-F group (2.6% vs 5.4%). Toxicity related dropout, treatment delay and/or further BCG dose reduction, and need for symptomatic drugs were similar. Moderate to severe local side effects during induction were higher in the BCG-F group (6.2% vs 16.9%) but equilibrated during maintenance therapy. Systemic reactions were rare. CONCLUSIONS: This multicenter trial provides a benchmark for the efficacy and safety of combination BCG and IFN as up front and salvage therapy. The incremental value of IFN cannot be determined from this study.	bladder
Partial cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection.	PURPOSE: Partial cystectomy is a bladder sparing procedure that has been used to treat invasive bladder cancer in highly selected patients. This study analyzes the outcomes of partial cystectomy in a contemporary cohort of patients to identify appropriate selection criteria for the procedure. MATERIALS AND METHODS: Records were reviewed for 58 patients with a primary bladder tumor who had undergone partial cystectomy at Memorial Sloan-Kettering Cancer Center from 1995 to 2001. Information was collected on tumor size, histology, location, presence of carcinoma in situ (CIS), multifocality, neoadjuvant treatment, clinical stage, pathological stage and disease status. RESULTS: For the 58 patients analyzed, overall 5-year survival was 69% with a mean followup of 33 months (range 1 to 83). Of the patients 43 (74%) are alive with an intact bladder, 39 (67%) are currently disease-free with an intact bladder and 32 (55%) have been continuously disease-free with an intact bladder. Seven patients experienced a superficial recurrence and were treated successfully while 15 patients experienced an advanced recurrence. On univariate analysis CIS and multifocality were related to superficial recurrence, and lymph node involvement and positive surgical margin were related to advanced recurrence. On multivariate analysis concomitant CIS (odds ratio 7.05, p = 0.004) and lymph node involvement (odds ratio 4.38, p = 0.031) were predictors of advanced recurrence. CONCLUSIONS: In highly selected patients with invasive bladder cancer, partial cystectomy offers acceptable outcomes. Concomitant CIS and presence of metastases to regional lymph nodes predict advanced recurrence.	bladder
Metastasis markers in bladder cancer: a review of the literature and clinical considerations.	Cancer invasion and metastasis develop through a sequence of processes involving loss of cell-cell and cell-matrix adhesions, proteolysis and induction of angiogenesis. We reviewed the current literature on the molecules that have been shown to play a significant role in these three steps of metastatisation in bladder cancer (BC) cells and their host microenvironment. Particular emphasis was given to markers that are assessable through immunohistochemistry and for which an additional prognostic value over the TNM variables has been recognized, in order to identify a subset of tumour markers readily available for application in daily clinical practice. We conclude that markers such as E-cadherin, Sialosyl-LeX, laminin, collagen IV, TSP-1 and MVD are useful prognostic markers, alpha, beta, and gamma catenin, MMP-2 and -9, uPAR, PD-ECGF and Bfgf can be considered potentially useful, while research on CD44, MMP-1 and -3, uPA, cathepsin D and VEGF has proved inconclusive. Further research in this field should concentrate on the molecules listed in the first group.	bladder
Determination of diagnostic and prognostic values of urinary interleukin-8, tumor necrosis factor-alpha, and leukocyte arylsulfatase-A activity in patients with bladder cancer.	OBJECTIVES: This study was planned to evaluate the feasibility of the assay of leukocyte arylsulfatase-A (AS-A) activity, and some urinary cytokine levels (tumor necrosis factor-alpha [TNF-alpha] and interleukin-8 [IL-8]), as noninvasive diagnostic tools in different stages of bladder cancer patients. DESIGN AND METHODS: Blood and urine samples of 79 subjects were analyzed, including 28 healthy volunteers, 27 patients with superficial bladder cancer (SBC), and 24 patients with muscle invasive bladder cancer (MIBC). RESULTS: In SBC patients, the mean leukocyte AS-A activity was slightly higher (11.4%) than healthy subjects without reaching statistical significance. On the other hand, the enzyme activity in MIBC patients was significantly higher than those of controls (38.9%) and SBC patients (18.3%). Urinary TNF-alpha levels in both cancer groups were not significantly different from the control group. Urinary IL-8 levels of MIBC patients were significantly increased when compared with the levels of SBC patients and healthy subjects (P < 0.001). CONCLUSIONS: Based on our results, it may be concluded that measurement of leukocyte AS-A activity is not a sufficiently reliable noninvasive diagnostic test in distinguishing early stage bladder cancer from healthy subjects as well as detecting disease progression. Whereas measurement of urinary IL-8 may be valuable as a noninvasive diagnostic and prognostic test especially in patients with advanced bladder cancer. It also appears that complementary biochemical information may be obtained about the prognosis of the disease by monitoring urinary IL-8 profile. However, further confirmatory clinical trials about the prognostic value of the measurement of urinary IL-8 are needed.	bladder
Fluorescence cystoscopy and bladder surveillance.	PURPOSE OF REVIEW: Update on new developments in the field of fluorescence cystoscopy. RECENT FINDINGS: New agents are being studied to improve the accuracy of fluorescence cystoscopy. Hexyl-5-aminolevulinic acid is an ester form of 5-aminolevulinic acid with improved uptake by tumor cells. It has been shown to have higher specificity than 5-aminolevulinic acid and can possibly play a complementary role to standard cystoscopy. Hypericin is a promising new agent that has excellent sensitivity and specificity. The use of confocal microscopy to examine fluorescent tissue may help improve the accuracy. SUMMARY: The addition of newer agents to the armamentarium of fluorescence cystoscopy has great potential with promising results in improving the diagnostic accuracy of bladder cancer and in particular carcinoma in situ. These agents need to be studied in large randomized trials to prove that using these agents can facilitate early diagnosis and improved prognosis in patients with bladder cancer.	bladder
New molecular markers for bladder cancer detection.	PURPOSE OF REVIEW: Bladder cancer continues to be one of the most common genitourinary malignancies. The mainstay of diagnosis remains cystoscopic visualization with transurethral biopsy or resection. As over two-thirds of bladder tumors recur, vigilant surveillance is required. Due to the invasiveness and expense of frequent cystoscopies and the lack of sensitivity of urinary cytology, especially for low-grade superficial lesions, novel molecular markers have been investigated as a means to detect bladder cancer noninvasively. RECENT FINDINGS: As our understanding of the pathogenesis of urothelial neoplasia improves, coupled with recent advances in molecular biological techniques, an array of new approaches to the diagnosis of bladder cancer has emerged. Several urine-based markers have been tested against the standard of urinary cytology with promising results. However, lack of standardization of technique and heterogeneity of bladder cancer itself may hinder the widespread dissemination of these diagnostic aids. SUMMARY: A host of new molecular markers based on the pathogenesis of bladder cancer have been investigated, such as telomerase, survivin, and multitarget fluorescence in situ hybridization, which may eventually improve detection and management of urothelial malignancies. By improving the sensitivity of urinary cytology for low-grade superficial lesions and detecting recurrent disease noninvasively early in its course, these new molecular markers might someday allow changes in the way bladder cancer is diagnosed and followed. At the present time, however, no single molecular marker provides 100% accuracy. Perhaps panels utilizing the most promising of these markers may alter bladder cancer detection and management policy.	bladder
The immunohistochemical assessment of hypoxia, vascularity and proliferation in bladder carcinoma.	BACKGROUND AND PURPOSE: Hypoxia and proliferation are important determinants of radiation responsiveness; prospective measures of these before radiotherapy may enable individualisation of treatment schedules. Immunohistochemical techniques offer a potential means of achieving this in routine biopsy material. MATERIAL AND METHODS: Cellular hypoxia as measured by pimonidazole fixation and immunohistochemistry has been evaluated in a series of human bladder cancers with dual staining of sections for pimonidazole and either the vascular markers, CD31/34, or proliferation markers, Ki-67 or cyclin A. Twenty one tumour specimens were examined suitable for the double staining technique. RESULTS: The median hypoxic fraction was 9% (range 0-38). Seven tumours did not stain for pimonidazole and 11 exhibited necrosis. The mean vascular density ranged from 16.7 to 160.6 vessels per mm2. The median hot spot count was 30 (range 16-43). There was a statistically significant increase in vessel density in hypoxic compared to oxic regions measured by both vessel density (P = 0.02) and hot spot count (P = 0.004). Proliferation indices decreased from oxic to hypoxic areas close to blood vessels. CONCLUSIONS: We have demonstrated that bladder cancer exhibits a range of hypoxia, proliferation and vascular density which may be used to form the basis for patient selection for hypoxia modification, accelerated radiotherapy and vascular targeting agents.	bladder
Long-term bladder, colorectal, and sexual functions after radical radiotherapy for urinary bladder cancer.	PURPOSE: To describe bladder, colorectal, and sexual dysfunctions among long time survivors after radical radiotherapy for urinary bladder cancer, and compare the results with a healthy control group. MATERIALS AND METHODS: We identified 261 patients who had received radical radiotherapy for bladder cancer in the period 1994-2001. Patients were treated with a CT-based three-field technique with 60 Gy in 2 Gy fractions, 5 fractions/week. Sixty-two patients were alive and candidates for the study. For comparison, 185 controls were selected from the Danish National Register. Information was collected in an interview based on the LENT SOMA tables and questions concerning changes in daily life following radiotherapy. RESULTS: Fifty-three patients (85%), median age 77 years (range 51-84) entered the study. Median follow-up time was 29 months (range 18-103 months). There were 63 controls (34%). Fourteen percent of the patients reported that radiotherapy had moderate to severe impact on their present bladder function. Compared with the control group, significantly more patients had dysuria, and urethral stenosis, and were using bladder catheter. Twenty-nine percent of the patients reported moderate to severe impact on their present bowel function. Significantly more patients had diarrhoea, fecal urgency and fecal incontinence, and were using antidiarrhoea medication and sanitary pads. Twenty-five percent of the patients reported moderate to severe impact on their present sexual function. Impotence and lack of sexual desire were significantly higher among the male patients. CONCLUSIONS: Following radical radiotherapy, most patients had a well functioning bladder, whereas 14% reported moderate to severe bladder dysfunctions. Due to the presence of bowel in the treatment field, radiotherapy is associated with considerable long-term intestinal side effects. Moreover, radiotherapy may result in sexual dysfunctions.	bladder
Unusual cytologic findings in low grade papillary transitional cell carcinoma.	"OBJECTIVE: To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. STUDY DESIGN: We defined the following unusual cytologic findings as ""isolated, single cell pattern"": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. RESULTS: Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. CONCLUSION: Some LG-pTCCs show many single, atypical transitional cells."	bladder
Hypericin as a potential phototherapeutic agent in superficial transitional cell carcinoma of the bladder.	Photodynamic therapy (PDT) involves the local or systemic administration of a photosensitizing drug that, upon light irradiation and presence of oxygen, results in tissue damage such as tumor destruction. Hypericin, a hydroxylated phenanthroperylenequinone, is obtained from Hypericum perforatum plants. Hypericin exhibits a high fluorescence quantum yield, and its presence in the tissue can easily be visualized. Interestingly, when instilled into the human bladders, hypericin selectively accumulates in the bladder carcinoma lesions, with the specificity and sensitivity of detecting CIS reaching up to 98.5 and 93%, respectively. Due to this selective accumulation of hypericin in bladder carcinoma lesions, the compound is now used as a fluorescent diagnostic tool for superficial bladder cancer. However, hypericin is also a photosensitizer with a potent photocytotoxic activity. Taken together, these data indicate that hypericin could be used for whole bladder wall PDT of superficial bladder tumors. This review focuses on the more recent in vitro and in vivo evaluation of hypericin as a photodynamic agent in the treatment of superficial transitional cell carcinoma (TCC) bladder tumors.	bladder